Myeloproliferative disorders are a group of conditions that cause blood cells, e.g., platelets, white blood cells, and red blood cells, to grow or differentiate abnormally in the bone marrow. Myeloproliferative disorders typically include polycythemia vera, primary myelofibrosis, chronic myelogenous leukemia, and essential thrombocythemia. Polycythemia vera occurs when the bone marrow produces too many red blood cells. In cases of primary myelofibrosis (also known as idiopathic myelofibrosis or myeloid metaplasia), the bone marrow produces too much collagen and is replaced by fibrous tissue, reducing the ability of bone marrow to produce blood cells. Chronic myelogenous leukemia (CML) is a type of cancer of the bone marrow that produces too many granulocytes and their precursors in the bone marrow. Essential thrombocythaemia (also known as primary thrombocytosis) occurs when the body produces too many platelet cells, which help blood to clot; clots can block blood vessels, leading to heart attack or stroke. In some cases essential thrombocythemia is a progressive disorder which may evolve into acute myeloid leukemia or myelofibrosis.
Among the treatments for essential thrombocythemia is anagrelide ((6,7-dichloro-1,5-dihydroimidazo (2,1-b)quinazolin-2(3H)-one). Anagrelide is a potent inhibitor of phosphodiesterase type III. Anagrelide also inhibits the development of megakaryocytes and consequently platelet production. In certain patients anagrelide may have undesirable side effects ranging from mild to serious. Accordingly, additional agents that can inhibit the differentiation of megakaryocytes may offer improved therapeutic options.